• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Development of novel therapeutic strategies for uterine leiomyoma

Research Project

Project/Area Number 16K11107
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKanazawa University

Principal Investigator

Ono Masanori  金沢大学, 附属病院, 講師 (70348712)

Co-Investigator(Kenkyū-buntansha) 丸山 哲夫  慶應義塾大学, 医学部(信濃町), 准教授 (10209702)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2018: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords子宮筋腫 / 子宮 / 組織幹細胞 / 子宮筋 / 子宮筋腫幹細胞 / エストロゲン / プロゲステロン / 生殖医学
Outline of Final Research Achievements

Tissue-specific stem cells constitute a subset of cells residing in normal adult tissues. Estrogen and progesterone stimulate the growth of leiomyomas. Estrogen, together with its receptor ERα, enables progesterone action via induction of progesterone receptor expression. Progesterone induces the growth of leiomyoma by regulation of a set of key genes that control proliferation and apoptosis.The WNT/β-catenin pathway comprises a key component of this signaling system. The majority of medical treatments currently available for leiomyoma works by inhibiting estrogen or progesterone production or action, but tumors tend to regrow once treatment is stopped. We showed that uterine leiomyoma stem cells involve IGF2 and Insulin Receptor A. Targeting stem cells and their paracrine interactions with more differentiated cell populations within leiomyoma may lead to the development of more effective therapeutics for uterine leiomyoma.

Academic Significance and Societal Importance of the Research Achievements

子宮筋腫の発育に関わる因子として、これまで性ステロイド,Transforming growth factor-β/SMAD, Retinoic acid, PPARγが報告されてきた。今回我々は、ヒト子宮平滑筋の発生・分化・修復の機構とその異常、また子宮筋腫の病態メカニズムにWNT/β-cateninシグナル、IGF2とInsulin Receptor A のシグナルが関わっていることを明らかにした。これまで子宮筋腫の治療は性ステロイドに働きかけるものが使用され、使用終了後には子宮筋腫が増悪してしまっていたが、当研究成果によりは子宮筋腫の新たな効果的な治療薬開発に役立てることができる。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (43 results)

All 2019 2018 2017 2016 Other

All Int'l Joint Research (3 results) Journal Article (17 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 17 results,  Open Access: 9 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results) Book (7 results) Remarks (1 results)

  • [Int'l Joint Research] ノースウェスタン大学(米国)

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research]

    • Related Report
      2017 Research-status Report
  • [Int'l Joint Research] ノースウェスタン大学(米国)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Twin anemia-polycythemia sequence with blood chimerism in monochorionic dizygotic opposite-sex twins2019

    • Author(s)
      Suzuki Takuma、Kagami Kyosuke、Mitani Yusuke、Yamazaki Rena、Ono Masanori、Fujiwara Hiroshi
    • Journal Title

      Journal of Obstetrics and Gynaecology Research

      Volume: 2019 Issue: 6 Pages: 1-4

    • DOI

      10.1111/jog.13949

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Factors Regulating Human Extravillous Trophoblast Invasion: Chemokine-peptidase and CD9-integrin Systems2018

    • Author(s)
      Fujiwara Hiroshi、Matsumoto Hisanori、Sato Yukiyasu、Horie Akihito、Ono Masanori、Nakamura Mitsuhiro、Mizumoto Yasunari、Kagami Kyosuke、Fujiwara Tomoko、Hattori Akira、Maida Yoshiko、Daikoku Takiko、Imakawa Kazuhiko、Araki Yoshihiko
    • Journal Title

      Current Pharmaceutical Biotechnology

      Volume: 19 Issue: 10 Pages: 764-770

    • DOI

      10.2174/1389201019666181029164906

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Three-dimensional evaluation of murine ovarian follicles using a modified CUBIC tissue clearing method.2018

    • Author(s)
      Kagami K., Shinmyo Y., Ono M., Kawasaki H. and Fujiwara H.
    • Journal Title

      Reproductive Biology and Endocrinology

      Volume: 16 Issue: 1 Pages: 72-72

    • DOI

      10.1186/s12958-018-0381-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Time Restriction of Food Intake During the Circadian Cycle Is a Possible Regulator of Reproductive Function in Postadolescent Female Rats.2018

    • Author(s)
      Fujiwara T, Nakata R, Ono M, Mieda M, Ando H, Daikoku T, Fujiwara H.
    • Journal Title

      Curr Dev Nutr

      Volume: 3 Issue: 4 Pages: 1-7

    • DOI

      10.1093/cdn/nzy093

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Successful detection of SRY gene via fine needle biopsy: A case of extragenital gestational choriocarcinoma in the kidney2017

    • Author(s)
      Orisaka Shunsuke、Kagami Kyosuke、Mizumoto Yasunari、Koda Wataru、Ono Masanori、Nakamura Mitsuhiro、Fujiwara Hiroshi
    • Journal Title

      MOLECULAR CLINICAL ONCOLOGY

      Volume: 7 Pages: 1057-1060

    • DOI

      10.3892/mco.2017.1460

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Dual expression of immunoreactive estrogen receptor β and p53 is a potential predictor of regional lymph node metastasis and postoperative recurrence in endometrial endometrioid carcinoma2017

    • Author(s)
      Obata Takeshi、Nakamura Mitsuhiro、Mizumoto Yasunari、Iizuka Takashi、Ono Masanori、Terakawa Jumpei、Daikoku Takiko、Fujiwara Hiroshi
    • Journal Title

      PLOS One

      Volume: 12 Issue: 11 Pages: 0188641-0188641

    • DOI

      10.1371/journal.pone.0188641

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Subserous invasion of VEGF-C-producing cancer cells is a possible risk factor for ileal ulceration in the non-metastatic mucosal layer during bevacizumab-combined chemotherapy for recurrent ovarian cancer: A case report2017

    • Author(s)
      Matsumoto Takeo、Mizumoto Yasunari、Nakade Kyohei、Obata Takeshi、Matsuoka Ayumi、Myojo Subaru、Ono Masanori、Nakamura Mitsuhiro、Fujiwara Hiroshi
    • Journal Title

      MOLECULAR CLINICAL ONCOLOGY

      Volume: 7 Issue: 5 Pages: 820-824

    • DOI

      10.3892/mco.2017.1403

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Three-dimensional visualization of intrauterine conceptus through the uterine wall by tissue clearing method2017

    • Author(s)
      Kagami Kyosuke、Shinmyo Yohei、Ono Masanori、Kawasaki Hiroshi、Fujiwara Hiroshi
    • Journal Title

      SCIENTIFIC REPORTS

      Volume: 7 Issue: 1 Pages: 5964-5964

    • DOI

      10.1038/s41598-017-06549-6

    • NAID

      120006374152

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Giant fetal hydrometrocolpos associated with cloacal anomaly causing postnatal respiratory distress2017

    • Author(s)
      Kanda Tatsuhito、Iizuka Takashi、Yamazaki Rena、Iwadare Junpei、Ono Masanori、Fujiwara Hiroshi
    • Journal Title

      JOURNAL OF OBSTETRICS GYNAECOLOGY RESEARCH

      Volume: 43 Issue: 11 Pages: 1769-1772

    • DOI

      10.1111/jog.13433

    • NAID

      120006343947

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] APOBEC3G is increasingly expressed on the human uterine cervical intraepithelial neoplasia along with disease progression2017

    • Author(s)
      Iizuka Takashi、Wakae Kousho、Nakamura Mitsuhiro、Kitamura Koichi、Ono Masanori、Fujiwara Hiroshi、Muramatsu Masamichi
    • Journal Title

      AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY

      Volume: 78 Issue: 4 Pages: 111-111

    • DOI

      10.1111/aji.12703

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Platelet-derived microparticles and soluble factors differentially regulate human endometrial epithelial cell movement2017

    • Author(s)
      Suginami K, Sato Y, Horie A, Matsumoto H, Tani H, Mizumoto Y, Ono M, Matsuoka A, Kyo S, Araki Y, Konishi I, Fujiwara H
    • Journal Title

      Am J Reprod Immunol

      Volume: Feb 7 Issue: 4 Pages: 12641-12641

    • DOI

      10.1111/aji.12641

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Paracrine Pathways in Uterine Leiomyoma Stem Cells Involve Insulinlike Growth Factor 2 and Insulin Receptor A2017

    • Author(s)
      Moravek Molly B.、Yin Ping、Coon John S.、Ono Masanori、Druschitz Stacy A.、Malpani Saurabh S.、Dyson Matthew T.、Rademaker Alfred W.、Robins Jared C.、Wei Jian-Jun、Kim J. Julie、Bulun Serdar E.
    • Journal Title

      JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM

      Volume: 102 Issue: 5 Pages: 1588-1595

    • DOI

      10.1210/jc.2016-3497

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Paracrine Pathways in Uterine Leiomyoma Stem Cells Involve Insulin-like Growth Factor-2 and Insulin Receptor-A2017

    • Author(s)
      Moravek MB, Yin P, Ono M, Coon JS 5th, Dyson MT, Navarro A, Marsh EE, Chakravarti D, Kim JJ, Wei JJ, Bulun SE
    • Journal Title

      THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Platelet-derived microparticles and soluble factors differentially regulate human endometrial epithelial cell movement2017

    • Author(s)
      Suginami K, Sato Y, Horie A, Matsumoto H, Tani H, Mizumoto Y, Ono M, Matsuoka A, Kyo S, Araki Y, Konishi I, Fujiwara H
    • Journal Title

      AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY

      Volume: 印刷中

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Short, severe dizziness attacks in a pregnant woman with type I ARNOLD-Chiari malformation2016

    • Author(s)
      Ono M, Kojima A, Shirahashi M, Noda S, Akiba Y, Nishijima S, Amagata T, Ikeda T, Yakubo K, Fukuiya T
    • Journal Title

      J Obstet Gynaecol

      Volume: 36 Pages: 430-431

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Dicephalus Parapagus Conjoined Twins Diagnosed by First-Trimester Ultrasound2016

    • Author(s)
      Watanabe K, Ono M, Shirahashi M, Ikeda T, Yakubo K
    • Journal Title

      Case Rep Obstet Gynecol.

      Volume: -

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Journal Article] Laparoscopic repair of an indirect inguinal hernia containing a fallopian tube in an adult woman2016

    • Author(s)
      Shirahashi M, Ono M, Yokoyama N, Okamoto N, Motomura Y, Ikeda T, Yakubo K
    • Journal Title

      Gynecology and minimally Invasive Therapy

      Volume: 5 Pages: 94-95

    • Related Report
      2016 Research-status Report
    • Peer Reviewed
  • [Presentation] 子宮頸部の炎症はAPOBEC3G発現を誘導しCINの進行に影響しうる2018

    • Author(s)
      飯塚 崇, 若江 亨祥, 中村 充宏, 小野 政徳, 村松 正道, 藤原 浩
    • Organizer
      日本性感染症学会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 生殖生物学研究のためのイメージング技術と応用 マウス妊娠子宮の透明化と3次元画像構築によるfetomaternal interfaceの解析2018

    • Author(s)
      鏡 京介, 小野 政徳, 飯塚 崇, 松本 多圭夫, 小幡 武司, 松岡 歩, 藤原 浩
    • Organizer
      日本組織細胞化学会総会・学術集会
    • Related Report
      2018 Annual Research Report
  • [Presentation] CRISPR/CAS9システムによりMED12変異を導入したヒト子宮筋腫モデルの開発の試み2018

    • Author(s)
      高尾 知佳, 丸山 哲夫, 小野 政徳, 内田 浩, 升田 博隆, 内田 明花, 三木 史恵, 片倉 慧美, 吉政 佑之, 藤原 浩, 田中 守, 青木 大輔
    • Organizer
      日本産科婦人科学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] APOBEC3Gの発現は子宮頸部異形成の進行に伴い上昇する2018

    • Author(s)
      飯塚 崇, 中村 充宏, 小野 政徳, 藤原 浩
    • Organizer
      日本産科婦人科学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 出生前より周産期良性型低ホスファターゼ症を疑い,出生後早期より酵素補充療法を開始した一例 診断から生後8ヵ月の経過2018

    • Author(s)
      石島 有華, 飯塚 崇, 小野 政徳, 山崎 玲奈, 保野 由紀子, 桝本 咲子, 鏡 京介, 岩垂 純平, 明星 須晴, 水本 泰成, 中村 充宏, 藤原 浩
    • Organizer
      日本産科婦人科学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 子宮体部類内膜癌におけるリンパ節転移および術後再発の予測因子の解析2018

    • Author(s)
      小幡 武司, 中村 充宏, 飯塚 崇, 小野 政徳, 水本 泰成, 藤原 浩
    • Organizer
      日本産科婦人科学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス妊娠子宮の透明化と内部構造の3次元画像構築2018

    • Author(s)
      鏡 京介, 飯塚 崇, 松本 多圭夫, 小幡 武司, 松岡 歩, 折坂 俊介, 岩垂 純平, 山崎 玲奈, 小野 政徳, 藤原 浩
    • Organizer
      日本産科婦人科学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] 続発性無月経の診断と治療2018

    • Author(s)
      小野 政徳
    • Organizer
      日本産科婦人科学会学術講演会
    • Related Report
      2018 Annual Research Report
  • [Presentation] マウス妊娠子宮の透明化と3次元画像構築2017

    • Author(s)
      鏡 京介, 小野 政徳, 新明 洋平, 河崎 洋志, 藤原 浩
    • Organizer
      日本生殖医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] マウス卵巣顆粒膜細胞におけるActivation induced cytidine deaminase(AID)の発現の検討2017

    • Author(s)
      飯塚 崇, 若江 享祥, 喜多村 晃一, 小野 政徳, 村松 正道, 藤原 浩
    • Organizer
      日本生殖医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 母体の血中hCG異常高値を示し,甲状腺の機能異常をきたした巨大胎盤血管腫の1例2017

    • Author(s)
      山崎 玲奈, 桝本 咲子, 岩垂 純平, 保野 由紀子, 飯塚 崇, 鏡 京介, 小野 政徳, 藤原 浩
    • Organizer
      日本周産期・新生児医学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 胎児腹水の原因と大網浮遊像の所見についての検討2017

    • Author(s)
      飯塚 崇, 山崎 玲奈, 保野 由紀子, 桝本 咲子, 三谷 裕介, 酒井 清祥, 岩崎 秀紀, 鏡 京介, 小野 政徳, 藤原 浩
    • Organizer
      北日本産科婦人科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] 研修病院におけるJoel-Cohen変法による帝王切開術の有用性についての検討2017

    • Author(s)
      鈴木 拓馬, 小野 政徳, 鏡 京介, 飯塚 崇, 桝本 咲子, 保野 由紀子, 山崎 玲奈, 藤原 浩
    • Organizer
      北日本産科婦人科学会
    • Related Report
      2017 Research-status Report
  • [Presentation] Role of stem cells in pathophysiology of uterine leiomyoma2016

    • Author(s)
      Ono M, Maruyama T, Tanaka M, Aoki D, Bulun SE
    • Organizer
      5th Asian Conference on Endometriosis
    • Place of Presentation
      Osaka
    • Year and Date
      2016-09-22
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Somatic Stem Cells in the Myometrium and Tumor-Initiating Cells in Leiomyomas2016

    • Author(s)
      Ono M, Maruyama T, Tanaka M, Aoki D, Bulun SE
    • Organizer
      The 8th Japan-Korea ART Conference
    • Place of Presentation
      Yokohama
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research
  • [Book] Uterine Fibroids and Adenomyosis2018

    • Author(s)
      Masanori Ono, Tetsuo Maruyama, Hiroshi Fujiwara, Serdar E. Bulun
    • Total Pages
      173
    • Publisher
      Springer
    • ISBN
      9789811071669
    • Related Report
      2018 Annual Research Report
  • [Book] 胎児発育不全2018

    • Author(s)
      小野 政徳、飯塚 崇、藤原 浩
    • Total Pages
      196
    • Publisher
      中外医学社
    • ISBN
      9784498060906
    • Related Report
      2018 Annual Research Report
  • [Book] 成人看護[3] 第14版2018

    • Author(s)
      石毛 尚代、小野政徳
    • Total Pages
      374
    • Publisher
      医学書院
    • ISBN
      9784260031790
    • Related Report
      2018 Annual Research Report
  • [Book] ホルモンQ&A ホルモン治療中の出血対策方法にはどのような方法がありますか2017

    • Author(s)
      小野 政徳, 藤原 浩
    • Total Pages
      3
    • Publisher
      HORMONE FRONTIER IN GYNECOLOGY
    • Related Report
      2017 Research-status Report
  • [Book] ホルモンQ&A 乳癌でホルモン治療中の若年女性患者を診察する際に留意すべきことを教えてください2017

    • Author(s)
      小野 政徳, 藤原 浩
    • Total Pages
      3
    • Publisher
      HORMONE FRONTIER IN GYNECOLOGY
    • Related Report
      2017 Research-status Report
  • [Book] 【万能幹細胞・幹細胞とゲノム編集-再生医療の進歩が医療を変える】産婦人科領域における再生医療とゲノム編集子宮筋幹細胞の臨床的意義2017

    • Author(s)
      小野 政徳, 丸山 哲夫, 田中 守
    • Total Pages
      5
    • Publisher
      臨床婦人科産科
    • Related Report
      2017 Research-status Report
  • [Book] 産科と婦人科 【子宮筋腫の最前線】 子宮筋腫の起源 幹細胞からの理解2016

    • Author(s)
      小野政徳、丸山哲夫、田中守
    • Total Pages
      5
    • Publisher
      診断と治療社
    • Related Report
      2016 Research-status Report
  • [Remarks] 金沢大学医薬保健研究域医学系産科婦人科学教室

    • URL

      http://obgyn.w3.kanazawa-u.ac.jp/introduction/dispensary/index.php

    • Related Report
      2018 Annual Research Report

URL: 

Published: 2016-04-21   Modified: 2022-02-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi